TY  - JOUR
A1  - Baur, Johannes
A1  - Otto, Christoph
A1  - Steger, Ulrich
A1  - Klein-Hessling, Stefan
A1  - Muhammad, Khalid
A1  - Pusch, Tobias
A1  - Murti, Krisna
A1  - Wismer, Rhoda
A1  - Germer, Christoph-Thomas
A1  - Klein, Ingo
A1  - Müller, Nora
A1  - Serfling, Edgar
A1  - Avots, Andris
T1  - The transcription factor NFaTc1 supports the rejection of heterotopic heart allografts
JF  - Frontiers in Immunology
N2  - The immune suppressants cyclosporin A (CsA) and tacrolimus (FK506) are used worldwide in transplantation medicine to suppress graft rejection. Both CsA and FK506 inhibit the phosphatase calcineurin (CN) whose activity controls the immune receptor-mediated activation of lymphocytes. Downstream targets of CN in lymphocytes are the nuclear factors of activated T cells (NFATs). We show here that the activity of NFATc1, the most prominent NFAT factor in activated lymphocytes supports the acute rejection of heterotopic heart allografts. While ablation of NFATc1 in T cells prevented graft rejection, ectopic expression of inducible NFATc1/αA isoform led to rejection of heart allografts in recipient mice. Acceptance of transplanted hearts in mice bearing NFATc1-deficient T cells was accompanied by a reduction in number and cytotoxicity of graft infiltrating cells. In CD8\(^+\) T cells, NFATc1 controls numerous intracellular signaling pathways that lead to the metabolic switch to aerobic glycolysis and the expression of numerous lymphokines, chemokines, and their receptors, including Cxcr3 that supports the rejection of allogeneic heart transplants. These findings favors NFATc1 as a molecular target for the development of new strategies to control the cytotoxicity of T cells upon organ transplantation.
KW  - NFATc1
KW  - transplantation
KW  - heterologous
KW  - CD8+ T cells
KW  - ChIPseq
KW  - metabolism
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221530
VL  - 9
ER  - 
TY  - JOUR
A1  - Pelz, Jörg O. W.
A1  - Wagner, Johanna
A1  - Lichthardt, Sven
A1  - Baur, Johannes
A1  - Kastner, Caroline
A1  - Matthes, Niels
A1  - Germer, Christoph-Thomas
A1  - Wiegering, Armin
T1  - Laparoscopic right-sided colon resection for colon cancer - has the control group so far been chosen correctly?
JF  - World Journal of Surgical Oncology
N2  - Background:
The treatment strategies for colorectal cancer located in the right side of the colon have changed dramatically during the last decade. Due to the introduction of complete mesocolic excision (CME) with central ligation of the vessels and systematic lymph node dissection, the long-term survival of affected patients has increased significantly. It has also been proposed that right-sided colon resection can be performed laparoscopically with the same extent of resection and equal long-term results.

Methods:
A retrospective evaluation of a prospectively expanded database on right-sided colorectal cancer or adenoma treated at the University Hospital of Wuerzburg between 2009 and 2016 was performed. All patients underwent CME. This data was analyzed alone and in comparison to the published data describing laparoscopic right-sided colon resection for colon cancer.

Results:
The database contains 279 patients, who underwent right-sided colon resection due to colorectal cancer or colorectal adenoma (255 open; 24 laparoscopic). Operation data (time, length of stay, time on ICU) was equal or superior to laparoscopy, which is comparable to the published results. Surprisingly, the surrogate parameter for correct CME (the number of removed lymph nodes) was significantly higher in the open group. In a subgroup analysis only including patients who were feasible for laparoscopic resection and had been operated with an open procedure by an experienced surgeon, operation time was significantly shorter and the number of removed lymph nodes is significantly higher in the open group.

Conclusion:
So far, several studies demonstrate that laparoscopic right-sided colon resection is comparable to open resection. Our data suggests that a consequent CME during an open operation leads to significantly more removed lymph nodes than in laparoscopically resected patients and in several so far published data of open control groups from Europe. Further prospective randomized trials comparing the long-term outcome are urgently needed before laparoscopy for right-sided colon resection can be recommended ubiquitously.
KW  - colon cancer
KW  - laparoscopic right colectomy
KW  - lymph nodes
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176186
VL  - 16
IS  - 117
ER  -